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Latest Research on Depression
     
Tijdschr Psychiatr. 2008;50(1):23-31.
[The efficacy of electroconvulsive therapy in adolescents. A restrospective study.]
[Article in Dutch]
Hegeman JM, Doesborgh SJ, van Niel MC, van Megen HJ.
BACKGROUND: Electroconvulsive therapy (ect) is an effective treatment for depressive disorders in adults and the elderly. For adolescents however, ect is still a controversial treatment because little research has been done into the efficacy and side effects of ect in adolescents and because psychiatrists working with children and adolescents are relatively unfamiliar with this form of treatment. AIM: To investigate the efficacy of ect in adolescents who were treated in Meerkanten between 2000 and 2006 for a therapy-resistant depressive episode and/or suicidal behaviour. METHOD: Scores on the Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale before and after ect were compared. The percentage improvement on the depression scales and the percentage of patients who showed an improvement of at least 60% on the scales in the group of adolescents were compared with the percentage improvement in a group of adults treated in Meerkanten. results One-third of the adolescent patients showed an improvement of 60% or more on these scales; the average improvement was 46%. ect was found to be equally effective in adolescents and adults. CONCLUSION: ect is a successful form of treatment for one-third of adolescents with a severe therapy-resistant depressive episode; this is a clinically relevant result for these patients for whom no alternative treatments are available.

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Am J Psychiatry. 2008 Jan 2 [Epub ahead of print]
Difference in Treatment Outcome in Outpatients With Anxious Versus Nonanxious Depression: A STAR*D Report.
Fava M, Rush AJ, Alpert JE, Balasubramani GK, Wisniewski SR, Carmin CN, Biggs MM, Zisook S, Leuchter A, Howland R, Warden D, Trivedi MH.

Objective About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study. Method A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression. Results In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options. Conclusions Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment.

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Am J Geriatr Psychiatry. 2008 Jan;16(1):14-20.
Escitalopram in the acute treatment of depressed patients aged 60 years or older.
Bose A, Li D, Gandhi C.
From Forest Research Institute, Jersey City, NJ.

Objective: The present study examined the efficacy and tolerability of acute escitalopram treatment in depressed patients aged 60 years or older. Methods: Patients aged >/=60 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive disorder were randomized to 12 weeks of double-blind, flexible-dose treatment with escitalopram (10-20 mg/day; N = 130) or placebo (N = 134). The prospectively defined primary efficacy end point was change from baseline to week 12 in Montgomery-Asberg Depression Rating Scale (MADRS) total score using the last observation carried forward approach. Results: A total of 109 (81%) patients in the placebo group and 96 (74%) patients in the escitalopram group completed treatment. Mean age in both groups was approximately 68 years. Mean baseline MADRS scores were 28.4 and 29.4 for the placebo and escitalopram treatment groups, respectively. Escitalopram did not achieve statistical significance compared with placebo
in change from baseline on the MADRS (least square mean difference: -1.34; last observation carried forward). Discontinuation rates resulting from adverse events were 6% for placebo and 11% for escitalopram. Treatment-emergent adverse events reported by >10% of patients in the escitalopram group were headache, nausea, diarrhea, and dry mouth. Conclusions: Escitalopram treatment was not significantly different from placebo treatment on the primary efficacy measure, change from baseline to week 12 in MADRS. In patients aged 60 years or older with major depression, acute escitalopram treatment appeared to be well tolerated.

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J Am Geriatr Soc. 2008 Jan 4 [Epub ahead of print]
Can Counseling and Support Reduce Burden and Depressive Symptoms in Caregivers of People with Alzheimer's Disease During the Transition to Institutionalization? Results from the New York University Caregiver Intervention Study.
Gaugler JE, Roth DL, Haley WE, Mittelman MS.
Center on Aging, Center for Gerontological Nursing, School of Nursing, University of Minnesota, Minneapolis, Minnesota, USA.

OBJECTIVES: To determine whether counseling and support reduce the burden and depressive symptoms of spouse caregivers of patients with Alzheimer's disease (AD) during the transition to institutionalization. DESIGN: A randomized, controlled trial of an enhanced counseling and support program for spouse caregivers of persons with AD. Structured interviews were conducted with spouse caregivers at baseline, every 4 months during Year 1, and every 6 months thereafter for up to 16 years. SETTING: Outpatient research clinic in the New York City metropolitan area. PARTICIPANTS: Referred volunteer sample of 406 spouse caregivers of community-dwelling patients with AD enrolled over a 9.5-year period. INTERVENTION: Enhanced counseling and support consisting of six sessions of individual and family counseling, support group participation, and continuous availability of ad hoc telephone counseling. MEASUREMENTS: Outcome measures included burden (modified Zarit Burden Interview) and depressive symptoms (Geriatric Depression Scale). RESULTS: Burden and depressive symptoms were significantly lower for caregivers in the treatment group than for controls receiving usual care at the time of and after institutionalization. Nursing home admission itself significantly reduced burden and depressive symptoms in the intervention and control groups. CONCLUSION: Institutionalization alone can reduce caregiver burden and depressive symptoms, but enhanced counseling provides additional long-term benefits. The results offer some of the first clinical evidence of the benefits of enhanced counseling during the transition to institutionalization for caregivers of people with AD.

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Psychol Med. 2008 Jan 4;:1-11 [Epub ahead of print]
Vagus nerve stimulation for depression: efficacy and safety in a European study.
Schlaepfer TE, Frick C, Zobel A, Maier W, Heuser I, Bajbouj M, O'Keane V, Corcoran C, Adolfsson R, Trimble M, Rau H, Hoff HJ, Padberg F, Müller-Siecheneder F, Audenaert K, Van den Abbeele D, Matthews K, Christmas D, Stanga Z, Hasdemir M.
Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, MD, USA.

BACKGROUND: Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. METHOD: An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. RESULTS: The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). CONCLUSIONS: VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

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Am J Geriatr Psychiatry. 2008 Jan;16(1):58-64.
Treatment Outcomes for Older Depressed Patients With Earlier Versus Late Onset of First Depressive Episode: A Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Report.
Kozel FA, Trivedi MH, Wisniewski SR, Miyahara S, Husain MM, Fava M, Lebowitz B, Zisook S, Rush AJ.
Department of Psychiatry, University of Texas Southwestern Medical Center (FAK, MHT, MMH, AJR), Dallas, TX; the Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh (SRW, SM), Pittsburgh, PA; the Department of Psychiatry, Harvard University, Massachusetts General Hospital (MF), Boston, MA; the Department of Psychiatry, University of California at San Diego (BL), San Diego, CA; the Department of Psychiatry, University of California at San Diego and San Diego VA Medical Center (SZ), La Jolla, CA; and the Department of Clinical Sciences, University of Texas Southwestern Medical Center (AJR), Dallas, TX.

Objective: Controversy exists whether age at onset of the first depressive episode predicts chance of response and remission or the timing of such outcome. In this study of older depressed outpatients, the authors evaluated whether the age at onset of the first major depressive episode (MDE) was related to clinical outcomes. Design: Post-hoc dataset analysis for older participants treated with citalopram in the Sequenced Treatment Alternatives to Relieve Depression trial was performed. Side effects, remission rates, and baseline characteristics were compared for participants whose first MDE began at or before age 55 (earlier onset) versus those with their first MDE after age 55 (late onset). Setting: Participants were enrolled from 23 psychiatric and 18 primary care settings. Participants: There were 574 treatment-seeking outpatients (age range: 55-75 years) with nonpsychotic major depressive disorder who had a baseline 17-item Hamilton Rating Scale for Depression score of >/=14. Intervention: Participants received citalopram treatment for up to 14 weeks. Measurements: Remission was defined by a 16-item Quick Inventory of Depressive Symptomatology-Self-Rated score of </=5 at study exit. Side effects were measured by the Frequency, Intensity, and Burden of Side Effects Rating. Results: Of 574 participants, 72.1% had earlier-onset depression and 27.9% had late-onset depression. Remission rates were not statistically different between earlier-onset (30.8%) and late-onset (31.9%) participants. Time to remission did not differ as well. Conclusion: The self-reported age at onset of the first MDE being after age 55 was not related to clinical outcomes for participants 55 to 75 years of age.

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Exp Clin Psychopharmacol. 2007 Dec;15(6):529-38.
Testosterone supplementation for depressed men: Current research and suggested treatment guidelines.
Kanayama G, Amiaz R, Seidman S, Pope HG.
Biological Psychiatry Laboratory, McLean Hospital.

Several lines of accumulating evidence suggest that testosterone might be effective for the treatment of depression, especially in older men who exhibit low testosterone levels. However, despite the potential promise of this approach, the available literature of controlled studies of testosterone in depression remains extremely limited. Therefore, testosterone treatment of depression must still be considered an experimental procedure. At the present state of research, it appears that testosterone might most likely show benefit as an augmentation strategy in men who exhibit low or borderline testosterone levels and who show only a partial response to conventional antidepressants. In this article, we provide some suggested practical guidelines for the treatment of such individuals. However, it should be recognized that these suggestions are tentative and will likely require revision as additional data become available. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

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J Manag Care Pharm. 2007 Nov;13(9 Suppl A):S3-11.
Quest for timely detection and treatment of women with depression.
Alexander JL.
Psychiatry Women's Health Program, Kaiser Permanente, Northern California, Oakland, USA. Jeanne@afwh.org

BACKGROUND: Women are at risk for a wide range of depressive and anxiety disorders and particularly for mood disorders associated with their menstrual cycle, with seasonality, and during the menopausal transition. OBJECTIVE: To review the presentation of depression, the importance of timely and effective treatment, and some of the research surrounding increased prevalence of depression in women, and the times and conditions--such as the perimenopausal transition, pregnancy, postpartum period, and comorbidities--of this increased risk in women. SUMMARY: Dynamic interactions of both biological and environmental factors contribute to the development of major depression. These include, but are not limited to, predisposing genetic influences, gender, environmental stressors, poor social support, childhood sexual abuse, other psychiatric illness, and trauma. Timely and effective treatment of each episode of depression to remission is critically important. Barriers to instituting collaborative care of depressive illness are numerous. The lack of adequate collaborative care along with the consequent failure to adequately diagnose and treat depression reflects some of the deficiencies in the current organization and delivery of health services. CONCLUSION: The prevalence of depression, its psychosocial and medical consequences, and the worsening course of depression without treatment highlight the public health importance of early detection and improved strategies for the treatment of depression in modern health care settings.

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Nervenarzt. 2007 Nov;78 Suppl 3:551-63; quiz 564.
[Pharmacological therapy for therapy-resistant depression. New developments]
[Article in German]
Tadic A, Lieb K.
Klinik für Psychiatrie und Psychotherapie, Johannes-Gutenberg-Universität, Untere Zahlbacher Strasse 8, 55131 , Mainz. tadic@psychiatrie.klinik.uni-mainz.de

Remission, i.e. the complete absence of symptoms, is the major goal in the treatment of major depressive disorders because residual symptoms cause less functioning and a worse outcome. Despite several treatment steps, numerous patients do not reach complete remission of symptoms. In these patients, it is necessary to rule out several possible causes, including inadequate pharmacotherapy, to confirm the diagnosis of treatment-resistant depression (TRD). In the treatment of TRD, pharmacotherapy plays a central role. Nonpharmacological treatment strategies such as psychotherapy, electroconvulsive therapy, and other brain stimulation methods are also used for TRD treatment and are discussed elsewhere in this issue. Regarding complex pharmacotherapy of TRD, only a limited number of randomized-controlled trials have been done. In consequence, treatment decisions are often based on clinical experience, case series, and uncontrolled studies. Nevertheless, there are some interesting n
ew developments, which are summarized and assessed on the basis of existing evidence in this article. Afore, we present an overview of the most important definitions, epidemiologic data, diagnostic needs and methods for treatment optimization. We end with a critical view on the present and future development of antidepressant drugs.

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J ECT. 2007 Sep;23(3):169-74.
A questionnaire study of patients' experience of electroconvulsive therapy.
Myers DH.
From the Shelton Hospital, Shrewsbury, UK.

OBJECTIVE:: To ascertain patients' experience of electroconvulsive therapy (ECT) using a questionnaire having these features: short so to be acceptable to the elderly and the depressed; ascertaining experience, not opinions; coming from a 'neutral' source; and analyzed by methods that do not impose an arbitrary scale on ordinal response categories. METHOD:: Two hundred eighty-eight traceable patients consecutively treated with ECT were surveyed, the majority by post. One hundred forty-eight replied. RESULTS:: The conviction, a median of 4 years after ECT, that side effects persisted was related to current depression and, inversely, to age, but not to the number of ECT given. Current depression was also associated with a less favorable account of emotional support during ECT. Formal legal status had no effect on any of the answers, but refusal of, or agreement to ECT on sufferance, was linked to a relatively unfavorable view of it. Not all patients regarded the decision to give them ECT compulsorily wrong on principle; some judged by results. CONCLUSIONS:: The degree of current depression contributes to several aspects of the patient's view of ECT given a median of 4 years earlier. The belief that side effects persist has a complex basis; but the importance of this belief is not thereby diminished. Legal compulsion of treatment adds its own quota of contention which can be mitigated, but not entirely dispelled, by careful adherence to the law.

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J ECT. 2007 Sep;23(3):153-157.
Changes in Everyday and Semantic Memory Function After Electroconvulsive Therapy for Unipolar Depression.
Schat A, van den Broek WW, Mulder PG, Birkenhäger TK, van Tuijl R, Murre JM.
From the *Department of Psychology, University of Amsterdam, Amsterdam and Departments of †Psychiatry and ‡Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands.

OBJECTIVES:: This long-term prospective study focuses on the effects of electroconvulsive therapy (ECT) on everyday memory function and on semantic memory function. METHODS:: Results of memory test from 96 consecutive inpatients treated for unipolar depression were analyzed prospectively before ECT, after ECT treatment, and at 3- and 12-month follow-up. Everyday memory function was assessed by means of the Rivermead Behavioural Memory Test (RBMT) and semantic memory by 2 forms of the word fluency test. RESULTS:: In our study, age had a constant and significant negative effect on everyday memory (RBMT score) over time. Bilateral electrode placement mainly influenced everyday memory, which was significantly improved at 3-month follow-up. One year after discharge, the RBMT scores were not significantly different from pretreatment levels, indicating that ECT does not affect everyday memory on the longer term.Scores on both word fluency tests for semantic memory were significantly influenced by age over time. The effect of age changed from a negative influence directly after ECT to a positive effect at follow-up. This advantage of higher age indicates that the semantic memory of older patients receiving ECT for severe mood disorder shows greater improvement at follow-up compared with younger patients. Over time, the scores on only 1 of the word fluency tests were significantly influenced by mainly bilateral electrode placement. CONCLUSIONS:: A small but reversible decrease in everyday memory occurs after ECT in depressed patients, which is influenced by age and electrode placement. Semantic memory shows a fluctuating but recovering course, which is also influenced by age and electrode placement. During follow-up, the improvement in semantic memory was greater in the older patients.

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Am J Med. 2007 Sep;120(9):799-806.
Impact of cardiac rehabilitation on depression and its associated mortality.
Milani RV, Lavie CJ.
Department of Cardiology, Ochsner Medical Center, New Orleans, La 70121, USA. rmilani@ochsner.org

PURPOSE: Depression following major cardiac events is associated with higher mortality, but little is known about whether this can be reduced through treatment including cardiac rehabilitation and exercise training. We evaluated the impact of cardiac rehabilitation on depression and its associated mortality in coronary patients. PATIENTS AND METHODS: We evaluated 522 consecutive coronary patients (381 men, 141 women; aged 64+/-10 years) enrolled in cardiac rehabilitation from January 2000 to July 2005 and a control group of 179 patients not completing rehabilitation. Depressive symptoms were assessed by questionnaire at baseline and following rehabilitation, and mortality was evaluated after a mean follow-up of 1296+/-551 days. RESULTS: Prevalence of depressive symptoms decreased 63% following rehabilitation, from 17% to 6% (P <.0001). Depressed patients following rehabilitation had an over 4-fold higher mortality than nondepressed patients (22% vs 5%, P=.0004). Depressed patients who completed rehabilitation had a 73% lower mortality (8% vs 30%; P=.0005) compared with control depressed subjects who did not complete rehabilitation. Reductions in depressive symptoms and its associated mortality were related to improvements in fitness; however, similar reductions were noted in those with either modest or marked increases in exercise capacity. CONCLUSION: In patients following major coronary events, cardiac rehabilitation is associated with both reductions in depressive symptoms and the excess mortality associated with it. Moreover, only mild improvements in levels of fitness appear to be needed to produce these benefits on depressive symptoms and its associated mortality.

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J Am Geriatr Soc. 2007 Sep;55(9):1325-1332.
Maintenance Treatment for Old-Age Depression Preserves Health-Related Quality of Life: A Randomized, Controlled Trial of Paroxetine and Interpersonal Psychotherapy.
Dombrovski AY, Lenze EJ, Dew MA, Mulsant BH, Pollock BG, Houck PR, Reynolds CF 3rd.
Western Psychiatric Institute and Clinic, Department of Psychiatry, School of Medicine, University of Pittsburgh, and Advanced Center for Interventions and Services Research in Late-Life Mood Disorders, and John A. Hartford Center for Excellence in Geriatric Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

OBJECTIVES: To determine whether maintenance antidepressant pharmacotherapy and interpersonal psychotherapy sustain gains in health-related quality of life (HR-QOL) achieved during short-term treatment in older patients with depression. DESIGN: After open combined treatment with paroxetine and interpersonal psychotherapy, responders were randomly assigned to a two (paroxetine vs placebo) by two (monthly interpersonal psychotherapy vs clinical management) double-blind, placebo-controlled maintenance trial. HR-QOL outcomes were assessed over 1 year. SETTING: University-based clinic. PATIENTS: Of the referred sample of 363 persons aged 70 and older with major depression, 210 gave consent, and 195 started acute treatment; 116 met criteria for recovery, entered maintenance treatment, and were included in this analysis. INTERVENTIONS: Paroxetine; monthly manual-based interpersonal psychotherapy. MEASUREMENTS: Overall HR-QOL as measured using the Quality of Well-Being Scale (QWB) and six specific HR-QOL domains derived from the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) subscales. RESULTS: All domains of HR-QOL except physical functioning improved with successful acute and continuation treatment. After controlling for any effects of psychotherapy, pharmacotherapy was superior to placebo in preserving overall well-being (P=.04, effect size (r)=0.23), social functioning (P=.02, r=0.27), and role limitations due to emotional problems (P=.007, r=0.30). Interpersonal psychotherapy (controlling for the effects of pharmacotherapy) did not preserve HR-QOL better than supportive clinical management. CONCLUSION: Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall well-being achieved with treatment response in late-life depression. No such benefit was seen with interpersonal psychotherapy.

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Am J Psychiatry. 2007 Sep;164(9):1348-55.
Adjunctive Antidepressant Use and Symptomatic Recovery Among Bipolar Depressed Patients With Concomitant Manic Symptoms: Findings From the STEP-BD.
Goldberg JF, Perlis RH, Ghaemi SN, Calabrese JR, Bowden CL, Wisniewski S, Miklowitz DJ, Sachs GS, Thase ME.
128 East Avenue, Norwalk, CT 06851. JFGoldberg@yahoo.com.

OBJECTIVE: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. METHOD: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by >/=2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. RESULTS: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. CONCLUSIONS: In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy.

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Ann Clin Psychiatry. 2007 Jul-Sep;19(3):187-95.
The efficacy and tolerability of duloxetine in the treatment of anxious versus non-anxious depression: a post-hoc analysis of an open-label outpatient study.
Fava M, Martinez JM, Greist J, Marangell LB, Brown E, Chen L, Wohlreich MM.
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Background. This study compares the efficacy and tolerability of 12 weeks of open-label duloxetine in adult outpatients with anxious versus non-anxious depression. Methods. Participants in a major depressive episode (N = 249) began duloxetine treatment at 30 or 60 mg daily for the first week, followed by up to 11 weeks of flexibly dosed duloxetine (60, 90, or 120 mg daily). Efficacy measures included HAMD(17), HAMA, and CGI-S. Safety and tolerability were assessed by early discontinuation and adverse event rates. Anxious depression was defined by a HAMD(17) Anxiety/Somatization Factor score >/= 7. Results. Duloxetine treatment was associated with a significantly greater reduction in total HAMD(17) scores and HAMD(17) Anxiety/Somatization Factor scores among patients with anxious depression compared to non-anxious depression. Differences in CGI-S and HAMA scores at the end of the trial between groups were not statistically significant. Remission and response rates at endpoint
were similar between groups, but anxious depressives had a significantly shorter median time to response. Discontinuation rates due to any reason, discontinuation due to adverse events, and treatment-emergent adverse events were similar between groups, except for the significantly greater occurrence of influenza in anxious depressives. Conclusions. Duloxetine's efficacy in anxious depression was somewhat superior to non-anxious depression; tolerability was comparable between groups.

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J Child Adolesc Psychopharmacol. 2007 Aug;17(4):407-20.
Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression.
Bangs ME, Emslie GJ, Spencer TJ, Ramsey JL, Carlson C, Bartky EJ, Busner J, Duesenberg DA, Harshawat P, Kaplan SL, Quintana H, Allen AJ, Sumner CR.
Lilly Research Laboratories, Indianapolis, Indiana.

This double-blind study examined efficacy and safety of atomoxetine (ATX; </=1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, >/=1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, >/= 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent:Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/
- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD.

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Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 3; [Epub ahead of print]
Open-label study of s-citalopram therapy of chronic fatigue syndrome and co-morbid major depressive disorder.
Amsterdam JD, Shults J, Rutherford N.
Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.

OBJECTIVE: Chronic fatigue syndrome (CFS) is a debilitating disorder with prominent symptoms of malaise, fatigue, myalgia, arthralgia, and impaired concentration. The symptoms of CFS may often overlap those of Major Depressive Disorder (MDD). Treatment of CFS has generally been disappointing. We hypothesized that s-citalopram therapy may improve the symptoms of both disorders in CFS patients with co-morbid depression. METHODS: 16 patients received s-citalopram 10 mg to 20 mg daily for up to 12 weeks. Outcome measures of CFS included the Chalder Fatigue Questionnaire (CFQ), the multi-dimensional Fatigue Impact Scale (FIS), the CFS symptom rating (CFS-SR) 100 mm visual analogue scale, and the clinical global impressions severity (CGI/S) and change (CGI/C) ratings. Secondary outcomes of MDD included the Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and the CGI/S and CGI/C ratings of MDD. RESULTS: We observed reductions in the mean CFQ score (p<0.0005), FIS score (p<0.0005), and CGI/S (p<0.0005) and CGI/C (p<0.0005) ratings over time. There was a significant improvement in 5 of the 8 CFS-SR symptoms: post-exertion malaise (p=0.001), headaches (p<0.0005), un-refreshing sleep (p<0.0005), and impaired memory and concentration (p<0.0005). There was also a reduction in mean HAM-D (p<0.0005), BDI (p<0.0005), CGI/S (p=0.001) and CGI/C (p<0.0005) ratings of MDD. LIMITATIONS: The sample size was limited and the study design was not double-blind or placebo controlled. CONCLUSION: We observed a significant reduction in both CFS and co-morbid MDD symptom severity ratings, and improvement in 5 of 8 core somatic symptoms of CFS during s-citalopram therapy.

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Behav Res Ther. 2007 Jul 24; [Epub ahead of print]
Sudden gains in interpersonal psychotherapy for depression.
Kelly MA, Cyranowski JM, Frank E.
Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O’Hara Street, Pittsburgh, PA 15213, USA.

Sudden, precipitous improvements in depressive symptom severity have been identified as occurring among unipolar depressed individuals. These "sudden gains" have been associated with superior acute treatment outcome in several treatment modalities, including cognitive therapy. A better understanding of sudden gains may provide insight into the mechanisms of action in these and other psychotherapies. One efficacious therapy that has been overlooked in sudden gains research is interpersonal psychotherapy (IPT; Weissman, M. M., Markowitz, J. C., & Klerman, G. L. (2000). Comprehensive guide to interpersonal psychotherapy. New York: Basic Books). The present research examined the rates and concomitant features of sudden, precipitous improvements in depressive symptomotology among 185 women receiving IPT for recurrent depression. Sudden gains, defined using extant criteria for the Beck Depression Inventory, were assessed over 12 weeks of acute IPT treatment for depression and occurred for 33.5% of the sample. Sudden gains were not associated with diagnostic and demographic characteristics or with differential likelihood of achieving depression remission with IPT monotherapy during active treatment. Further, those with sudden gains were no more likely to maintain their recovery through maintenance treatment. The lack of impact of sudden gains on eventual outcome is discussed in terms of potentially disparate emphases and mechanisms of change between IPT and cognitive-behavioral therapy (CBT).

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Int J Neuropsychopharmacol. 2007 May 4;:1-13 [Epub ahead of print]
Efficacy of agomelatine, a MT1/MT2 receptor agonist with 5-HT2C antagonistic properties, in major depressive disorder.
Pierre Olie J, Kasper S.
Sainte Anne Hospital, University Department of Psychiatry, Paris, France.

Current antidepressants used in major depressive disorder (MDD) are still not efficacious enough for many patients due to high levels of treatment resistance and bothersome side-effects. Using a novel blinding method (interactive voice response system), this flexible-dosing study examined the effects of therapeutic doses of agomelatine, a new approach to depressive therapy offering potent melatonergic MT1/MT2 receptor agonism with 5-HT2C receptor antagonist properties, in patients with moderate-to-severe MDD. This 6-wk, double-blind, parallel-group study randomized 238 patients to 25 mg/d agomelatine (with dose adjustment at 2 wk to 50 mg/d in patients with insufficient improvement) or placebo. Depression severity was assessed using the Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression (CGI) scale. Agomelatine was significantly more efficacious than placebo, with an agomelatine-placebo difference of 3.44 (p<0.001) using the HAMD final total score. Compared with placebo, agomelatine also had a significant positive impact on CGI - Improvement (treatment difference=0.45) and CGI - Severity (treatment difference=0.50) (both p=0.006), response rate (54.3% vs. 35.5% with placebo, p<0.05) and time to first response (p=0.008). Similar results were seen in patients with the most severe MDD. Depressed mood and sleep items of the HAMD were also significantly improved with agomelatine, which was well tolerated with a safety profile similar to placebo at both doses. This study confirms that agomelatine is effective in treating major depression, including the most severely depressed patients, with a good safety and tolerability profile, therefore providing physicians with an effective pharmacological approach to antidepressant therapy.

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Med Health Care Philos. 2007 May 3; [Epub ahead of print]
Do antidepressants affect the self? A phenomenological approach.
Svenaeus F.
Center for Studies in Practical Knowledge, Department of Philosophy, Sodertorn University College, Huddinge, 141 89, Sweden, fredrik.svenaeus@sh.se.

In this paper, I explore the questions of how and to what extent new antidepressants (selective serotonin-reuptake inhibitors, or SSRIs) could possibly affect the self. I do this by way of a phenomenological approach, using the works of Martin Heidegger and Thomas Fuchs to analyze the roles of attunement and embodiment in normal and abnormal ways of being-in-the-world. The nature of depression and anxiety disorders - the diagnoses for which treatment with antidepressants is most commonly indicated - is also explored by way of this phenomenological approach, as are the basic structures of self-being. Special attention is paid in the analysis to the moods of boredom, anxiety and grief, since they play fundamental roles in depression and anxiety disorders and since their intensity and frequency appear to be modulated by antidepressants. My conclusion is that the effect of these drugs on the self can be thought of in terms of changes in self-feeling, or, more precisely, self-vibration of embodiment. I present the idea of a spectrum of bodily resonance, which extends from the normal resonance of the lived body, in which the body is able to pick up a wide range of different moods; continuing over various kinds of sensitivities, preferences and idiosyncrasies, in which certain moods are favored over others; to cases that we unreservedly label pathologies, in which the body is severely out of tune, or even devoid of tune and thus useless as a tool of resonance. Different cultures and societies favor slightly differently attuned self-styles as paradigmatic of the normal and good life, and the popularity of the SSRIs can therefore be explained, not only by defects of embodiment, but also by the presence of certain cultural norms in our contemporary society.

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Am J Psychiatry. 2007 May;164(5):768-77.
An intensive treatment program of interpersonal psychotherapy plus pharmacotherapy for depressed inpatients: acute and long-term results.
Schramm E, van Calker D, Dykierek P, Lieb K, Kech S, Zobel I, Leonhart R, Berger M.
University Medical Center Freiburg, Department of Psychiatry and Psychotherapy, Hauptstrasse 5, 79104 Freiburg, Germany. Elisabeth.Schramm@uniklinik-freiburg.de.

OBJECTIVE: The purpose of this article was to determine the relative efficacy of a psychotherapy program when combined with pharmacotherapy versus medication and clinical management in more severely depressed patients. METHOD: A randomized controlled trial was conducted in 124 hospitalized patients with DSM-IV major depressive disorder that compared 5 weeks of interpersonal psychotherapy modified for depressed inpatients (15 individual and eight group sessions) plus pharmacotherapy with a regimen that involved medication plus intensive clinical management. The study included a prospective, naturalistic follow-up 3 and 12 months after acute treatment in 97 of 105 treatment completers. The 17-item version of the Hamilton Depression Rating Scale (HAM-D) was the primary outcome measure. RESULTS: For the intent-to-treat cohort (N=124), analysis of covariance (ANCOVA) showed that patients treated with interpersonal psychotherapy had a significantly greater reduction of depressive symptoms at week 5. Response rates differed significantly between the two treatment conditions, favoring the group that received adjuvant interpersonal psychotherapy (70%) versus clinical management (51%). Remission rates also tended to be higher for patients in the interpersonal psychotherapy group (49% versus 34%). Patients who initially responded to interpersonal psychotherapy exhibited greater treatment gains at the 3-month follow-up evaluation, since only 3% of these subjects relapsed, compared with 25% of the clinical management subjects. Nine months later, this difference lost statistical significance. CONCLUSIONS: An inpatient treatment program with both brief and intensive psychotherapy plus pharmacotherapy is superior to standard treatment. The results, which add to a growing body of evidence, suggest that this combination treatment may offer an advantage over treatment with medication and clinical management for more severely depressed patients.

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Am J Psychiatry. 2007 May;164(5):761-767.
Randomized Trial of Weekly, Twice-Monthly, and Monthly Interpersonal Psychotherapy as Maintenance Treatment for Women With Recurrent Depression.
Frank E, Kupfer DJ, Buysse DJ, Swartz HA, Pilkonis PA, Houck PR, Rucci P, Novick DM, Grochocinski VJ, Stapf DM.
Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213. franke@upmc.edu.

OBJECTIVE: The authors sought to determine whether a greater frequency of interpersonal psychotherapy (IPT) sessions during maintenance treatment has a greater prophylactic effect than a previously validated once-a-month treatment. METHOD: A total of 233 women 20-60 years of age with recurrent unipolar depression were treated in an outpatient research clinic. After participants had achieved remission with weekly IPT or, if required, with weekly IPT plus antidepressant pharmacotherapy, they were randomly assigned to weekly, twice-monthly, or monthly maintenance IPT monotherapy for 2 years or until a recurrence of their depression occurred. RESULTS: Among participants who remitted with IPT alone and entered maintenance treatment (N=99), 19 (26%) of the 74 who remained in the study throughout the 2-year maintenance phase experienced a recurrence of depression. Among participants who required the addition of a selective serotonin reuptake inhibitor to achieve remission (N=90), 32 (36%) sustained that remission through continuation treatment and drug discontinuation and began maintenance treatment; of these, 13 (50%) of the 26 who remained in the study throughout the maintenance phase experienced a recurrence. Survival analysis of time to recurrence by randomized treatment frequency showed no effect on recurrence-free survival in either treatment subgroup. CONCLUSIONS: These results suggest that maintenance IPT, even at a frequency of only one visit per month, is a good method of prophylaxis for women who can achieve remission with IPT alone. In contrast, among those who require the addition of pharmacotherapy, IPT monotherapy represents a significantly less efficacious approach to maintenance treatment.

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Am J Psychiatry. 2007 May;164(5):753-60.
Acceptability of Second-Step Treatments to Depressed Outpatients: A STAR*D Report.
Wisniewski SR, Fava M, Trivedi MH, Thase ME, Warden D, Niederehe G, Friedman ES, Biggs MM, Sackeim HA, Shores-Wilson K, McGrath PJ, Lavori PW, Miyahara S, Rush AJ.
Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, 127 Parran Hall, 130 DeSoto St., Pittsburgh, PA 15261. wisniew@edc.pitt.edu.

OBJECTIVE: Treatment of major depressive disorder typically entails implementing treatments in a stepwise fashion until a satisfactory outcome is achieved. This study sought to identify factors that affect patients' willingness to accept different second-step treatment approaches. METHOD: Participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who had unsatisfactory outcomes after initial treatment with citalopram were eligible for a randomized second-step treatment trial. An equipoise-stratified design allowed participants to exclude or include specific treatment strategies. Analyses were conducted to identify factors associated with the acceptability of the following second-step treatments: cognitive therapy versus no cognitive therapy, any switch strategy versus any augmentation strategy (including cognitive therapy), and a medication switch strategy only versus a medication augmentation strategy only. RESULTS: Of the 1,439 participants who entered second-step treatment, 1% accepted all treatment strategies, 3% accepted only cognitive therapy, and 26% accepted cognitive therapy (thus, 71% did not accept cognitive therapy). Those with higher educational levels or a family history of a mood disorder were more likely to accept cognitive therapy. Participants in primary care settings and those who experienced a greater side effect burden or a lower reduction in symptom severity with citalopram were more likely to accept a switch strategy as compared with an augmentation strategy. Those with concurrent drug abuse and recurrent major depressive disorder were less likely to accept a switch strategy. CONCLUSIONS: Few participants accepted all treatments. Acceptance of cognitive therapy was primarily associated with sociodemographic characteristics, while acceptance of a treatment switch was associated with the results of the initial treatment.

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Am J Psychiatry. 2007 May;164(5):739-752.
Cognitive Therapy Versus Medication in Augmentation and Switch Strategies as Second-Step Treatments: A STAR*D Report.
Thase ME, Friedman ES, Biggs MM, Wisniewski SR, Trivedi MH, Luther JF, Fava M, Nierenberg AA, McGrath PJ, Warden D, Niederehe G, Hollon SD, Rush AJ.
University of Pittsburgh Medical Center, 3811 O'Hara St., Pittsburgh, PA 15213-2593. thaseme@upmc.edu.

OBJECTIVE: The authors compared the effectiveness of cognitive therapy and pharmacotherapy as second-step strategies for outpatients with major depressive disorder who had received inadequate benefit from an initial trial of citalopram. Cognitive therapy was compared with medication augmentation and switch strategies. METHOD: An equipoise-stratified randomization strategy was used to assign participants to either augmentation of citalopram with cognitive therapy (N=65) or medication (N=117; either sustained-release bupropion [N=56] or buspirone [N=61]) or switch to cognitive therapy (N=36) or another antidepressant (N=86; sertraline [N=27], sustained-release bupropion [N=28], or extended-release venlafaxine [N=31]). Treatment outcomes and the frequency of adverse events were compared. RESULTS: Less than one-third of participants consented to randomization strata that permitted comparison of cognitive therapy and pharmacotherapy. Among participants who were assigned to second-step treatment, those who received cognitive therapy (either alone or in combination with citalopram) had similar response and remission rates to those assigned to medication strategies. For those who continued on citalopram, medication augmentation resulted in significantly more rapid remission than augmentation with cognitive therapy. Among those who discontinued citalopram, there were no significant differences in outcome, although those who switched to a different antidepressant reported significantly more side effects than those who received cognitive therapy alone. CONCLUSIONS: After an unsatisfactory response to citalopram, patients who consented to random assignment to either cognitive therapy or alternative pharmacologic strategies had generally comparable outcomes. Pharmacologic augmentation was more rapidly effective than cognitive therapy augmentation of citalopram, whereas switching to cognitive therapy was better tolerated than switching to a different antidepressant.

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J Clin Psychiatry. 2007 Apr;68(4):582-7.
Addition of atomoxetine for depression incompletely responsive to sertraline: a randomized, double-blind, placebo-controlled study.
Michelson D, Adler LA, Amsterdam JD, Dunner DL, Nierenberg AA, Reimherr FW, Schatzberg AF, Kelsey DK, Williams DW.
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Ind., USA. david_michelson@merck.com

OBJECTIVE: Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported. METHOD: Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks. RESULTS: Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/ atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p = .865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups. CONCLUSION: In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo.

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J Consult Clin Psychol. 2007 Apr;75(2):267-76.
Progressive resistance to a selective serotonin reuptake inhibitor but not to cognitive therapy in the treatment of major depression.
Leykin Y, Amsterdam JD, DeRubeis RJ, Gallop R, Shelton RC, Hollon SD.
Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104-6196, USA. leykin@psych.upenn.edu

Recent research suggests that there may be a reduction in therapeutic response after multiple administrations of antidepressant drug (AD) therapy in patients with major depressive disorder. This study assessed the response to AD therapy and cognitive therapy (CT) of patients with a history of prior AD exposures. A sample of 240 patients with moderate-to-severe major depressive disorder entered a randomized controlled trial comparing pharmacotherapy with paroxetine to CT. Treatment was administered for 16 weeks. History of prior AD exposure was assessed with structured interviews, self-report, and medical records. Analyses were conducted using hierarchical linear models on the intent-to-treat sample. After controlling for various demographic and clinical factors, more prior AD exposures predicted poor response to paroxetine therapy but not to CT, as measured by the Hamilton Rating Scale for Depression (Hamilton, 1960; Williams, 1988). Whereas CT outcome was not significantly related to the number of prior AD exposures, a higher number of prior AD exposures was significantly associated with a lower response to paroxetine. If these findings are replicated in methodologically rigorous studies of paroxetine and other antidepressants, CT should be recommended, in preference to AD, for patients with multiple prior AD exposures. Copyright 2007 APA, all rights reserved.

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Community Ment Health J. 2007 Jan 19; [Epub ahead of print]
The Trauma Recovery Group: A Cognitive-Behavioral Program for Post-Traumatic Stress Disorder in Persons with Severe Mental Illness.
Mueser KT, Bolton E, Carty PC, Bradley MJ, Ahlgren KF, Distaso DR, Gilbride A, Liddell C.
Department of Psychiatry, Dartmouth Medical School, New Hampshire-Dartmouth Psychiatric Research Center, 105 Pleasant St., Concord, NH, 03301, USA, kim.t.mueser@dartmouth.edu.

To address the problem of post-traumatic stress disorder (PTSD) in severe mental illness, the Trauma Recovery Group, a mixed gender cognitive-behavioral program, was developed and piloted at a community mental health center. The 21-week program includes breathing retraining, education about PTSD, cognitive restructuring, coping with symptoms, and making a recovery plan. Eighty clients were assessed at baseline and 41 provided follow-up data. Retention in the group was good: 59%. Treatment completers improved significantly in PTSD symptoms and diagnosis, depression, and post-traumatic cognitions, but dropouts did not. The results support the feasibility of the program and suggest it produces clinical benefits.

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J Am Geriatr Soc. 2007 Jan;55(1):75-80.
Treatment and prevention of depression after surgery for hip fracture in older people: randomized, controlled trials.
Burns A, Banerjee S, Morris J, Woodward Y, Baldwin R, Proctor R, Tarrier N, Pendleton N, Sutherland D, Andrew G, Horan M.
Division of Psychiatry, University of Manchester, Manchester, UK.

(See editorial comments by Drs. Barbara Kamholz and Jurgen Unutzer on pp 000-000.) OBJECTIVES: To evaluate the effect of a psychiatric intervention in treating depression (treatment study) and the effect of a psychological treatment in preventing depression (prevention study) after hip fracture in older people. DESIGN: Two linked randomized, controlled trials. SETTING: Orthopedic units in Manchester, England. PARTICIPANTS: Two hundred ninety-three older people who had undergone surgery for a fractured hip: 121 in the treatment study and 172 in the prevention study. MEASUREMENTS: The Geriatric Depression Scale and Hospital Anxiety and Depression Scale for mood, functional tests for mobility and pain measures. RESULTS: There was a slight reduction in depressive symptoms in the active arm of the treatment study. In the prevention study, there was no significant difference in incident depression between the psychological intervention and treatment as usual. There were no differences in the functional and pain outcomes. CONCLUSION: The results from these two randomized, controlled trials show that, after hip fracture surgery, no statistically significant benefits can be achieved from a psychiatric intervention in people who are depressed or a psychological intervention to prevent the onset of depression.

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Fortschr Neurol Psychiatr. 2007 Jan 17; [Epub ahead of print]
[Deep Brain Stimulation in the Treatment of Psychiatric Disorders.]
[Article in German]
Kuhn J, Huff W, Lee SH, Lenartz D, Sturm V, Klosterkotter J.
Klinik fur Psychiatrie und Psychotherapie, Klinikum der Universitat zu Koln.

As a well and long-established approach in the treatment of selected movement disorders, deep brain stimulation (DBS) is also increasingly considered a potential treatment method in the case of mental disorders. Only recently, a number of highly promising case reports and case series have been published, in which impressive therapeutic outcomes under application of DBS in otherwise treatment-resistant psychiatric illnesses are reported. The current article aims to provide a detailed synopsis of the DBS approach and more specifically its application to mental disorders. By means of a systematic literature search, all relevant treatment studies published to date and focusing on obsessive compulsive disorder, Tourette syndrome, major depression, anxiety disorder and autism were incorporated and evaluated with respect to the scientific evidence presented.

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Neuropsychobiology. 2007 Jan 17;54(3):152-159 [Epub ahead of print]
Escitalopram in the Long-Term Treatment of Major Depressive Disorder in Elderly Patients.
Kasper S, Lemming OM, de Swart H.
Medical University of Vienna, Vienna, Austria.

Aim: The primary aim was to investigate the long-term safety and tolerability of escitalopram (10 or 20 mg/day) treatment of elderly patients suffering from major depressive disorder. The secondary aim was to examine response to treatment, as measured by change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from study entry to each visit, using observed cases. Method: This extension trial included 225 patients who had completed an 8-week, double blind, placebo-controlled lead-in study, which was performed in outpatients in primary care and in specialist clinics. The intent-to-treat population comprised 223 patients. Results: The overall withdrawal rate was 24%. The most common reason for withdrawal was adverse events (9%). The 5 most common adverse events were accidental injury, rhinitis, weight increase, arthralgia and coughing, with an incidence ranging from 8 to 13%. No new types of adverse events were reported in this extension study compared to the 8-week lead-in study. The mean weight increased from 69.7 kg at study entry to 70.3 kg at endpoint. The percentage of patients in remission (MADRS total score </=12) increased from 48% at study entry to 72% by week 52. Conclusion: Escitalopram demonstrated a favourable tolerability profile during 52 weeks of open-label treatment of elderly patients, with further improvement in depressive symptoms. Copyright (c) 2006 S. Karger AG, Basel.

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J Affect Disord. 2007 Jan 15; [Epub ahead of print]
Open-label aripiprazole in the treatment of acute bipolar depression: A prospective pilot trial.
McElroy SL, Suppes T, Frye MA, Altshuler LL, Stanford K, Martens B, Leverich GS, Post RM, Keck PE Jr.
Psychopharmacology Research Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States.

BACKGROUND: Increasing evidence indicates that some second-generation antipsychotics are efficacious in bipolar depression, but there are few data on this illness for the novel agent aripiprazole. METHODS: Aripiprazole response was prospectively assessed for 8 weeks with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Scale Modified for Bipolar Illness (CGI-BP), and the Young Mania Rating Scale (YMRS) in 31 bipolar patients with acute depression inadequately responsive to 1 mood stabilizer. Side effects and body weight were also evaluated. Outcome measures were analyzed with repeated measures ANOVAs. RESULTS: Patients showed a significant decrease in mean MADRS total and CGI-BP-Depression Severity scores, but only 14 (45%) completed the 8-week trial. Thirteen (42%) patients met criteria for response (>/=50% reduction in MADRS total score), 11 (35%) patients met criteria for remission (final MADRS total score </=12), and 9 (29%) patients discontinued aripiprazole for side effects, most commonly akathisia (N=4). As a group, patients showed statistically insignificant weight gain (0.8+/-2.5 kg) over the 8-week trial. CONCLUSION: Aripiprazole was associated with beneficial effects on mood in some patients with bipolar depression, but also had a high discontinuation rate, primarily due to side effects. Double-blind, placebo-controlled studies are necessary to determine aripiprazole's efficacy, tolerability, and safety in bipolar depression.

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Prog Neuropsychopharmacol Biol Psychiatry. 2006 Dec 15; [Epub ahead of print]
Aripiprazole augmentation in treatment-resistant bipolar depression: Early response and development of akathisia.
Kemp DE, Gilmer WS, Fleck J, Straus JL, Dago PL, Karaffa M.
University Hospitals Case Medical Center, Case Western Reserve University, United States.

There is growing evidence that atypical antipsychotics may be effective in the treatment of acute bipolar depression. Results from randomized, placebo-controlled trials support the use of quetiapine monotherapy and a combination of olanzapine-fluoxetine in the depressed phase of bipolar disorder, while only limited data exists regarding the use of aripiprazole in this population. To assess the potential effectiveness of aripiprazole in treating acute bipolar depression, a chart review was conducted on 12 patients with treatment-resistant bipolar disorder (I, II, and not otherwise specified [NOS]) who received aripiprazole augmentation for the relief of an acute major depressive episode. After 8 weeks of treatment, 4 of 12 (33%) patients demonstrated a response, defined as a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score. In addition, 5 of 12 (42%) patients newly developed akathisia. This report, though limited by its small sample size and naturalistic design, suggests that the usefulness of aripiprazole in the treatment of bipolar depression may be limited by akathisia.
 

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